Inhibition of rat liver aminoacyl-tRNA synthetases in vitro after acute and chronic aflatoxin B1 administration in vivo.
In a cell-free system the influence of acute aflatoxin B1 administration on the fractions of the hepatic microsomal translation complex of female rats was examined and compared with the influence of chronic aflatoxin B1 treatment. Polypeptide synthesis determined by [14C]leucine incorporation with the postmitochondrial supernatant was inhibited by 80% 24 h after acute aflatoxin B1 administration whereas inhibition was only 17% in animals 30 weeks after chronic treatment. After acute aflatoxin B1 administration inhibition of protein synthesis was by 67%, mainly on the polysomal level, whereas inhibition with the pH 5 enzyme was only by 22%. After chronic aflatoxin B1 administration inhibition was by 18%, mainly with the pH 5 enzyme and by only 6% on the polysomes. The inhibition by pH 5 enzyme was further investigated with regard to aminoacyl-tRNA synthetases, components of pH 5 enzyme. Leucine-specific aminoacyl-tRNA synthesis was inhibited by 20% 24 h after acute and by 12% 30 weeks after chronic aflatoxin B1 treatment. Aminoacyl-tRNA synthetase activities in a crude synthetase preparation tested with 5 amino acids were found to be noncompetitively inhibited. It is concluded that the inhibition of protein synthesis after acute and chronic aflatoxin B1 administration is in part due to decreased aminoacyl-tRNA levels caused by inhibited aminoacyl-tRNA synthetases.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000633:toxicity*; D000604:Amino Acyl-tRNA Synthetases / Q000037:antagonists & inhibitors*; D000818:Animals; D002474:Cell-Free System / Q000187:drug effects; D005260:Female; D008099:Liver / Q000201:enzymology*; D014176:Protein Biosynthesis / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D000348:Aflatoxins; D016604:Aflatoxin B1; D000604:Amino Acyl-tRNA Synthetases